Coagulation and fibrinolysis are primary pathogenetic events in all thrombotic diseases and are frequently activated in association with the inflammatory response and blood vessel diseases. Fibrinolysis induced by plasmin cleavage of fibrin(ogen) leads to the generation of small peptides which suppress basic lymphocyte functions including DNA synthesis, protein synthesis and blastogenesis in vitro, and produce immune suppression when injected in vivo. These fibrinogen-derived peptides have also been demonstrated to regulate cellular activities of endothelial cells and platelets at physiologically attainable concentrations. The suppression of lymphocyte function appears to be mediated by a single discrete peptide, and the similarity in mechanism of action of the fibrinogen-derived peptides on endothelial cells and platelets is consistent with the hypothesis that a single bioregulatory peptide is generated by the fibrinolytic process. We propose to isolate and characterize the lymphocyte regulatory peptide and fibrinogen and to determine if this same peptide influences specific and specialized cellular functions of platelets, endothelial cells, neutrophils, macrophages, and smooth muscle cells. Molecular mechanisms by which this peptide modulated specific cellular functions will be elucidated, and the effects of the peptide when administered in vivo will be compared to alterations associated with the induction of fibrinolysis. With the development of a specific assay for the detection of this peptide, its role as a bioregulator in health and in disease will be evaluated and its physiologic significance ascertained.